3 Objectives Review the metabolism of arginineDemonstrate how disease alters the expression of the metabolic pathways.TraumaSepsisDetermine possible biological rolesIn healthIn diseaseEvaluate the clinical role of arginine supplementation.

10 The effect of Arginine infusion on Nitric oxide Production in ischemic flaps8 Pigs - Vascularized Pedicle Ischemic Flaps. Arginine given DURING the creation of the FlapNitric oxide production measured by chemiluminescence – microdialysisFlap viability using vital dyes

13 What is the Evidence? Harm vs. BenefitUnder Resting conditionsArginine is NOT used by the immune SystemNO mechanism of arginine transport into the cell.Enzymes that metabolize arginine NOT expressed.Therefore there is NO EVIDENCE that arginineIs an “IMMUNE ENHANCER”Dr. Bobbi Langkamp-Henken

26 Meta-analysis- Immune Enhancing Diets and Infectious ComplicationsHeyland D. JAMA 2001;(286)8:Taken as a whole indiscriminate use of IEDs is NOT indicated.IEDs ONLY work on disease processes where there is arginine DEFICIENCYThe Heyland meta-analysis looked at studies where the products had supplemental arginine as well as fish oil.This shows you how the immune restoring diets faired when compared to standard enteral diets in both elective surgery and critically ill patients.There’s a couple of take away points I want to leave you with here.#1, this data shows a clear indication for the use of high arginine diets in elective surgery and trauma patients.#2, this data has increased our awareness for the need to further study the application of these diets in septic patients.#3, if we are to meaningfully discuss and study the use of immune restoring diets in our patients we must drop the concept of ‘critical illness diet’ and talk specifically about surgery, trauma, and sepsis. Given what we know about arginine metabolism, critical illness is no longer a very useful term in discussing patient populations and the best diet to put them on.

28 Conclusions Arginine is Not an Immune EnhancerArginine is metabolized in a completely different way in health and diseaseChanges in arginine metabolism occur principally in the immune systemTrauma activates Myeloid cells to produce arginaseArginase depletes arginine & generates ornithineSepsis appears NOT to be associated with arginine deficiency

29 Conclusions Clinical EvidenceSurgery is benefited by the use of arginine, omega 3 fatty acids, and nucleotidesIdeally used 5 days preoperativelyOverall > 20 clinical Studies↓ 40% in infection ratesSignificant savingsTrauma Patients appear to benefit alsoModest number of patients

30 Conclusions Medical Critically Ill Patients are NOT benefited.No clear evidence of HarmSepsis Patients Controversial evidenceSome studies show HarmSome studies show benefitArginine-containing diets SHOULD NOT be used in these Patients

31 The Benefit or Harm of Arginine depends on How we use itThank you ASPEN